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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 685 records · Page 38Linked to original sources

Isolation and characterization of angiotensin I-converting enzyme inhibitory peptides derived from bonito bowels.

Four angiotensin I-converting enzyme (EC 3.4.15.1) (ACE) inhibitory peptides C105, C107, C111, and C112 were isolated from bonito bowels. C111 was obtained from liver, while the others were from intestine. Their amino acids were sequenced as Ser-Val-Ala-Lys-Leu-Glu-Lys for C105, Ala-Leu-Pro-His-Ala for C107, Gly-Val-Tyr-Pro-His-Lys for C111, and Ile-Arg-Pro-Val-Gln for C112. Their ACE inhibition activities were measured for synthetic peptides. The IC50 of these peptides were estimated to be 82, 79, 1.6, and 1.4 microM, respectively. Carboxyl-terminal amino acid(s) were considered to be essential for their expression of ACE inhibition for C105, C107, and C111, while the amino terminal tripeptide Ile-Arg-Pro of C112 was presumed to inhibit ACE after the removal of a dipeptide from C112 with ACE digestion. Presumed original proteins of these peptides are discussed.

Amino Acid Sequence↗

Angiotensin I-converting enzyme inhibitory peptides derived from bonito bowels autolysate.

Six angiotensin I-converting enzyme inhibitory peptides were isolated from a bonito bowels autolysate. Their amino acids were sequenced as Tyr-Arg-Pro-Tyr, Gly-His-Phe, Val-Arg-Pro, Ile-Lys-Pro, Leu-Arg-Pro, and Ile-Arg-Pro. Peptides having corresponding amino acid sequences were synthesized by a solid-phase method and their inhibition of the activity measured. IC50 of these peptides were estimated to be 320, 1100, 2.2, 2.5, 1.0, and 1.8 microM, respectively. The role of carboxyl terminal proline residues on the inhibition is discussed.

Amino Acid Sequence↗

Gonadotropin-releasing hormone increases serum human chorionic gonadotropin in pregnant women.

Hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH) has been found to stimulate human chronic gonadotropin (hCG) secretion by trophoblast cells in vitro. To determine the biological effect of GnRH on the release of hCG in vivo, we studied the effect of the administration of GnRH on the serum levels of human chronic gonadotropin (hCG) during pregnancy. Serum hCG levels were measured before and 15, 30, and 60 min after the intravenous administration of 100 micrograms of GnRH to 22 volunteers with normal pregnancy. Nine of the 12 (75%) women responded to GnRH in the first trimester, while only 1 of the 5 women (20%) responded to GnRH in the second trimester. None of the 5 women tested in the third trimester showed a significant response of hCG to the injection of GnRH. The average increase in hCG during the first, second and third trimester was 160.7 +/- 13.5%, 111.0 +/- 7.4% and 95.0 +/- 2.3%, respectively (mean +/- SEM). Whereas the pregnant courses of all the cases were uneventful and normal, other abnormal pregnancies were also investigated with informed consents. Three patients with missed abortions also showed a significant response of hCG to GnRH (increase: 136.7 +/- 8.5%) when GnRH was administered before curettage of the uterine cavity. However, 4 patients with unruptured ectopic pregnancies did not respond to GnRH stimulation. These findings indicate that GnRH can stimulate the release of hCG by the placenta in vivo, consistent with the previous in vitro study, while the responsiveness depend on gestational age and the implantation site.

Abortion, Missed↗

Inhibitory effects of insulin-like growth factor (IGF)-binding proteins-1 and -3 on IGF-activated glucose consumption in mouse BALB/c 3T3 fibroblasts.

We have examined the biological effects of insulin-like growth factor-binding proteins (IGFBPs) on insulin-like growth factor (IGF)-activated glucose consumption in a BALB/c 3T3 subline. The method employed was a colorimetric measurement of glucose consumption, allowing the detection of changes from the initial glucose concentration in conditioned medium, following the addition of IGFs and IGFBPs. Human IGFBP-1, purified from amniotic fluid, inhibited IGF-activated glucose consumption, although it had no effect on insulin-activated glucose consumption. The median effective dose (ED50) of IGFBP-1 to cause inhibitory effects on IGF-activated glucose consumption was 100-200 micrograms/l and was similar for both IGF-I and IGF-II at a concentration of 1.0 microgram IGF/l. Therefore, at IGF concentrations of comparable activity, the inhibitory effects of IGFBP-1 were greater for IGF-I than for IGF-II, because of the higher activity of IGF-I in this assay. Recombinant human IGFBP-3 also inhibited IGF-activated glucose consumption, without affecting insulin-stimulated glucose consumption. The inhibitory effects of IGFBP-3 were greater for IGF-II than for IGF-I when IGFBP-3 was coincubated with either of the IGFs, at both IGF concentrations of comparable activity and equivalent molar concentrations. Thus, it became clear that the inhibitory effects of these IGFBPs on IGF biological action depended primarily upon their affinity for the specific IGF ligand and molar ratio of IGFBP/IGF peptide. Interestingly, when cells were pretreated with IGFBP-3, prior to the simultaneous addition of IGFs and IGFBP-3, the inhibitory effect was higher for IGF-I than for IGF-II. Either no effect or a minor inhibitory effect on IGF-activated glucose consumption was detected with IGFBP pretreatment alone. When the ED50 for inhibition of IGF action by IGFBPs in this in-vitro assay was compared with the physiological concentrations of IGFs and IGFBPs in normal human serum and in amniotic fluid, it was estimated that the IGFBP-1 concentration present in serum was not sufficient to modulate IGF action effectively while the concentration in amniotic fluid was enough for effective suppression. IGFBP-3 exhibited an ED50 low enough to suppress IGF-II and possibly IGF-I action when cells were pretreated with IGFBP-3. Thus, our data suggested that IGFBP-1 in amniotic fluid and IGFBP-3 in serum could be a potent inhibitor for IGF action. IGFBP-1 in serum, however, may not be able to function as a direct inhibitor under physiological conditions but, rather, may modulate IGF action together with other IGFBPs.

Animals↗

The existence and distribution of melanocytes in the periodontal ligament of the mongrel dog.

The existence and distribution of melanocytes in the periodontal ligament of the mongrel dog were investigated. Melanocytes were found in the periodontal ligament of the maxillary incisor and premolar segments. Melanocytes in the periodontal ligament varied in number, and generally appeared as dendritic or elongated cells with several, long cytoplasmic processes. These melanocytes were always distributed closer to the tooth root side of the periodontal ligament than the alveolar bone side, but did not contact the cementum. Melanocytes were longitudinally distributed in the apical half of the periodontal ligament. There were no findings suggestive of a relationship between melanocytes and epithelial rests of Malassez or other cellular elements of the periodontal ligament. Although some parts of the gingival mucosa of all dogs in this study showed pigmentation, no relationship was seen between melanocytes in the periodontal ligament and those in the gingival mucosa. This is the first report of melanocytes in the periodontal ligament under normal conditions.

Animals↗

Hyperthermotherapy for postoperative local recurrences of rectal cancer.

Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected.

Adult↗

Multivariate analysis of magnetic resonance imaging of focal hepatic lesions.

A total of 124 lesions from 1 to 6cm in diameter, including 31 cavernous hemangiomas, 32 metastases and 61 hepatocellular carcinomas (HCC) were analyzed to study the usefulness of magnetic resonance imaging (MRI) at 0.5 Tesla to differentiate focal hepatic lesions on the basis of qualitative criteria. Each focal hepatic lesion was assessed for shape, internal architecture and signal intensity relative to normal liver parenchyma. While all cavernous hemangiomas and metastases except one lesion could be detected, detection rate of HCC was significantly inferior to that of the other two diseases. A tumor capsule and a hyperintense focus on T1-weighted images were demonstrated in only HCC lesions in strong contrast with the other two diseases; however, metastases with slow-growing characteristics or subacute hematoma may appear as similar images. Cavernous hemangiomas appeared markedly hyperintense on T2-weighted images in 23 of 31 lesions, but one metastasis and one HCC had similar images. A multivariate analysis of several MRI resulted in the following mean discriminant scores: cavernous hemangioma, -1.2652; metastasis, 0.1830; and HCC, 0.7138. It appeared to be possible to differentiate the three diseases with 84.4 percent accuracy.

Adult↗

Hyperthermotherapy added to the multidisciplinary therapy for penile cancer.

We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission.

Adult↗

Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C.

The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC-14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 micrograms/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 micrograms/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 micrograms/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA-VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA-VC.

Ascorbic Acid↗

[Single channel analysis of Ca2+ channel-agonistic action of dihydropyridine derivatives: voltage-dependent effects of YC-170 and BAY K 8644].

Voltage-dependent effects of YC-170, a dihydropyridine derivative, on rabbit cardiac L-type Ca2+ channels were investigated and compared with those of a dihydropyridine Ca2+ agonist, BAY K 8644, using patch clamp techniques. Single Ca2+ channel activities were elicited by depolarizing pulses to O mV from holding potentials (HPs) of -80 mV and -40 mV. With a HP of -80 mV, YC -170 (10 microM) increased a mean open time of the Ca2+ channel (vector o) from 0.50 +/- 0.03 ms to 1.2 +/- 0.05 ms (mean +/- S.E., n = 5), and increased NPo value of the Ca2+ channel by 710 +/- 96% (n = 5) of the control value. On the other hand, with a HP of -40 mV, YC-170 had little effects on NPo value (94 +/- 6.6% of the control value, n = 5), although YC-170 increased vector o from 0.64 +/- 0.05 ms to 1.2 +/- 0.11 ms. BAY K 8644 increased NPo values to almost the same degree with both HPs (920 +/- 93% with a HP of -80 mV, n = 5, and 990 +/- 85% with a HP of -40 mV, n = 5). BAY K 8644 (1 microM) remarkably increased vector o with both HPs (from 0.66 +/- 0.09 ms to 3.3 +/- 0.50 ms, n = 3, with a HP of -80 mV and from 0.68 +/- 0.06 ms to 4.9 +/- 1.2 ms, n = 4, with a HP of -40 mV). Although YC-170 and BAY K 8644 increased vector o with both HPs, YC-170 failed to produce the Ca2+ agonistic effect with less negative HP (-40 mV). Thus, another mechanism differing from prolongation of the open time may be involved in the agonistic action of YC-170. YC-170 increased markedly the frequency of openings of Ca2+ channels with a HP of -80 mV and decreased it with a HP of -40 mV. BAY K 8644 increased it slightly with a HP of -40 mV and did not change it with a HP of -80 mV. Analysis using closed time histograms also revealed that YC-170 enhanced reopenings of Ca2+ channels with a HP of 80 mV and suppressed it with a HP of -40 mV, BAY K 8644 enhanced it with both HPs. Two mechanisms may be involved in the agonistic action of dihydropyridine Ca2+ agonists. One is prolongation of the open time of Ca2+ channels and the other is an enhancement of reopenings of Ca2+ channels. The former mechanism may not be voltage dependent and the latter mechanism may be voltage dependent.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Role of growth factors on fetal growth and maturation.

Several growth factors have been demonstrated to be involved in fetal growth. In this study, physiological significance of two growth factors, epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on fetal growth was evaluated. IGF-I stimulated 3H-glycine uptake by cultured trophoblast cells from term pregnancy while EGF did not stimulate it. A large part of IGF-I was associated with its binding proteins (IGFBPs) in the circulation and one of IGFBPs, IGFBP-1 inhibited 3H-glycine uptake by IGF-I in a dose dependent manner. IGF-I also stimulated 3H-aminoisobutyric acid (3H-AIB) release by trophoblast cells when cells were saturated with 3H-AIB first, then stimulated with IGF-I. In animal experiments, placental weight but not fetal weight was suppressed when EGF antiserum was administrated to maternal mice, however, fetal lung maturity in terms of lamella body produced in type II alveolar cells was suppressed in antiserum given group. When anti IGF-I antiserum was administrated to pregnant mice, both fetal and placental weight were significantly suppressed and transfer of 3H-AIB to fetus was also suppressed. In contrast, antiserum to IGFBP-1 stimulated fetal growth and transfer of 3H-AIB to fetus. Furthermore, fetal lung on Day 17 in anti IGFBP-1 antiserum administrated mice showed morphologically advanced changes that were equivalent to Day 18 or 19 of control. These results indicate that EGF and IGF-I regulate fetal growth and maturation independently and that IGF-I and IGFBP-1 influence fetal development in a counter regulatory system.

Amino Acids↗

[Early and long-term results of sternocostal elevation combined with bridge external traction for funnel chest in children].

The purpose of the present study is to evaluate the effects of addition of a bridge external traction to our conventional sternocostal elevation technique in the surgical management of funnel chest in children. During the period from 1970 to 1979, a total of 29 children with funnel chest were treated surgically using sternocostal elevation technique (Group I). Operative technique consisted of total subperichondral resection of deformed costal cartilages (usually 3rd to 8th, bilaterally), transection of deformed portion of the sternum in 2-3 points and fixation of the sternum in elevated position using 2 Kirschner wires, and shortening resuturing of the opened perichondrium. Since 1980, an addition of the bridge external traction to our conventional sternocostal elevation technique was applied for about 10 days after operation in 82 consecutive children (Group II). The vertebral index (B/A = sagittal diameter of vertebral body/minimum sternovertebral distance), D/C ratio (maximum sagittal depth of depression of sternum/distance from anterior surface of the vertebral body to the sternum at Louis's angle) and E/C ratio (E = minimal sagittal distance from anterior surface of the vertebral body to the sternum) were measured in all cases and compared before and after operation and also between the two Groups. Preoperatively, there was no significant difference in all 3 indices between the two Groups. Postoperative B/A, D/C and E/C ratio in Group I were 0.28 +/- 0.06, 0.14 +/- 0.19, 1.09 +/- 0.32 (mean +/- SD), respectively. There were a significant drop in D/C ratio and a significant elevation in E/C ratio after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Changes in the blood flow in celiac artery and superior mesenteric artery after stellate ganglion block].

We evaluated the effect of stellate ganglion block (SGB) on the blood flow of celiac artery (CA) and superior mesenteric artery (SMA) by using the ultrasonic pulse Doppler technique. The subjects were 15 healthy volunteers (14 males, one female; average 26 years old; 22-38). Right C7-SGB was performed using 5 ml of 1% mepivacaine at the 7th cervical process. Blood pressure, heart rate, mean blood flow velocity and diameter in CA and SMA, were measured after 5 minute rest, before and after SGB. To measure the flow velocity and the diameter of vessels, ultrasonic diagnostic equipment SSA-270A or SSA-260A (Thoshiba CO, Ltd.) with convex electric-phased 3.75 MHz, probe was used. Doppler shiftgrams of the CA and SMA were recorded. Then, we calculated their flow volume and sectional area of vessels. In CA mean blood flow velocity tended to decrease (P < 0.05) and both flow volume and sectional area of vessels tended to increase (P < 0.001). In SMA, mean flow velocity tended to decrease (P < 0.05) and sectional area increased (P < 0.001). But flow volume did not show significant change. Our results indicate that right C7-SGB leads to an increase in the blood flow of CA.

Adult↗